Obesity is the most common nutritional disorder in North America;it develops when energy intake is greater than energy expenditure. The level of fat in the diet, together with portion size, is thought to play a major role in promoting the number of individuals who are obese. This emphasizes the need to understand the factors that are involved in modulating not only food intake but also the high preference for fat. Of the large number of peptides, neurotransmitters, and receptor populations that affect food intake, only a few have been demonstrated to make animals overeat and increase their fat preference. Included in this list are mu opioid receptors. The precise mechanism(s) by which mu opioid receptors make animals overeat and increase the preference for a high fat diet is unknown. What is know [sic] is that in obese animals, this receptor population is significantly increased in multiple areas of the central nervous system that are known to be involved in feeding behavior. We hypothesize that the increased mu opioid receptors are contributing to the overeating and increased fat preference that is observed in obese animals. The goals of this application are to determine 1)what causes mu opioid receptors to increase in obese animals;2)potential mechanisms by which mu opioid receptors make aniamls [sic] hyperphagic and increase fat preference;3)if increased mu opioid receptors potentiates the development of obesity. The results obtained from the studies can provide a potential target to attenuate the overeating and increased fat prefrence [sic] that is observed in humans that are obese. Our research plan will use a multi-disciplinary approach to allow the candiate [sic] of this K01 career development award to learn several techniques while testing the central hypothesis. Each aspect of the research plan will be conducted at Pennington Biomedical Research Center (Baton Rouge, LA). The sponsor (Dr. George A. Bray) and co-sponsors (Drs. Elizabeth Floyd, Gerlinda Hermann and Richard Rogers) along with a highly interactive basic and clinical research environment, will offer the candidate a great training opportunity to facilitate her transition into becoming a successful independent investigator. PUBLIC HEALTH RELEVANCE: Obesity accounts for approximately 100,000 to 300,000 deaths a year, making this disease the second-leading cause of death in the United States second only to smoking. This application will provide new insights into the cause of obesity and provide a target to help alleviate the development of this disease.